Describe common extrahepatic problems associated with chronic liver failure

Describe common extrahepatic problems associated with chronic liver failure.

A large number of extrahepatic problems are associated with ESLD, which may vary widely in severity and outcome.

Neurologic Problems

Changes in mental status are common but can be caused by a multitude of etiologies. Because there are pul-monary problems that are associated with ESLD, one should immediately rule out hypoxia or hypercardia as a cause for a change in mental status. Another life-threaten-ing but easily correctable etiology is hypoglycemia. Hepatic encephalopathy is common but not necessarily terminal. It readily responds to neomycin and lactulose therapy. Cerebral edema, although rare, is often a preterminal event that is associated with acute fulminant liver failure and must be treated aggressively. Treatment consists of con-trolled mechanical hyperventilation and administration of osmotic diuretics. Encephalopathic patients are at increased risk for regurgitation and aspiration of gastric contents. The clinician should have a very low threshold for elective endotracheal intubation to protect the airway. Other causes of changes in mental status include acidosis, sepsis, and increased side-effects of drugs secondary to increased drug levels due to changes in pharmacokinetics. Additionally, one should always be on the lookout for ingestion of alcohol and/or drugs by the patient.

Pulmonary Problems

Numerous pulmonary problems can occur in patients with progressive liver disease. As mentioned previously, patients with mental status changes are at risk for aspira-tion. Chronic cirrhotics frequently hyperventilate due to accumulation of ammonia or acidosis. Nevertheless, PaO₂ values of 60–70 mmHg are common in these patients. The diaphragmatic compression by massive ascites accounts for many of the pulmonary problems encoun-tered. This effectively reduces functional residual capacity (FRC) and predisposes to atelectasis and hypoxia. In addi-tion, complex changes in the pulmonary arterial bed can occur. Two clinically important and distinct pulmonary syndromes occur: hepatopulmonary syndrome and porto-pulmonary hypertension.

Hepatopulmonary Syndrome Arterial hypoxemia associ-ate with ESLD can be multifactorial. However, severe hypoxemia is likely secondary to hepatopulmonary syndrome. Capillary dilatation causes a diffusion defect (a decrease in pulmonary diffusion capacity). Additionally, right-to-left intrapulmonary shunts may develop, leading to a noncorrectable arterial hypoxemia. The shunts may be either secondary to atelectasis, alveoli that are filled with fluid and/or exudate, or direct arteriovenous channels.

Portopulmonary Hypertension Pulmonary hyperten-sion is not uncommon in advance liver disease. This can be a result of possible cardiac manifestations of (alcohol) cirrhosis, the hyperdynamic circulation that results in high pulmonary flows, or vasoconstriction, medial hypertrophy and intimal fibrosis leading to potentially irreversible pulmonary hypertension. The latter, when associated with portal hypertension, is known as portopulmonary hyper-tension and is considered indistinguishable from primary pulmonary hypertension. It should be noted that severe arterial hypoxemia is usually not associated with portopul-monary hypertension.

Cardiac Problems

Cardiac disease may be difficult to diagnose in these patients because of the debilitating nature of the liver disease. Alcohol cirrhotics can develop a cardiomyopathy, which can lead to congestive heart failure. However, ESLD results in massive peripheral vasodilation with a reduced systemic vascular resistance (SVR). This effectively lowers left ventricular work and allows for cardiac disease to exist without immediate symptoms. A heightened suspicion for the presence of cardiac impairment is warranted.

Patients with ESLD usually have a hyperdynamic circula-tion that is characterized by a high cardiac output and low SVR. The primary sites for the reduction in SVR are the splanchnic circulation and arteriovenous shunts, which are coupled with a decrease in the viscosity of blood secondary to anemia and the vasodilating effects of glucagon, vasoactive intestinal peptides (VIP), substance P, and prostaglandins. The combination of vasodilation and the formation of new arteriovenous channels results in an increase in the intravenous compartment. Fluid retention eventually increases the plasma volume; however, the larger increase in the intravascular compartment with respect to the increase in plasma volume results in a relative intravascular depletion.

Renal Problems

A host of abnormalities in renal function, ranging from mild renal insufficiency and electrolyte imbalances to hepatorenal syndrome, are common. Hepatorenal syn-drome usually occurs in the setting of severe liver disease without any obvious renal etiology. Cirrhosis can be associated with a decrease in the glomerular filtration rate (GFR) and renal blood flow (RBF) progressing to acute oliguria. Frequent problems resulting from aggres-sive treatment of ascites are prerenal azotemia and hypo-natremia. Because these patients usually have relative intravascular depletion, treatment is directed at intra-vascular volume replacement. Aggressive administration of salt-containing solutions is unwarranted unless required to maintain intravascular volume. Rapid correction of hyponatremia is dangerous and may result in central pontine myelinolysis and significant neurologic injury.

The pathogenesis of hepatorenal syndrome is incom-pletely understood. There is strong evidence to support the theory that the relative intravascular volume depletion is a major determinant of the initial renal hypoperfusion. Hormonal mechanisms have also been implicated. The kidney responds to intravascular depletion by increasing renin production, which causes constriction of the renal afferent arteries and fluid retention. Furthermore, produc-tion of renin goes unconstrained due to the decrease in the negative feedback from angiotensin I. In fact, patients with cirrhosis and impaired renal functions manifest the most profound elevations of renin. The physiologic ramifica-tions of this cycle are massive fluid retention, electrolyte abnormalities, and a possible role in the development of hepatorenal syndrome in ESLD.

Hematologic Problems

Other common extrahepatic problems in ESLD include a complex coagulopathy, which is in part due to decreased synthesis of clotting factors. Decreased production of platelets (decreased thrombopoietin), platelet sequestra-tion by the spleen, and disseminated intravascular coagula-tion (DIC) adversely complicate coagulation problems.

Metabolic Problems

Metabolic acidosis (metabolic alkalosis can be seen early in the disease process), whether due to renal dysfunction or the liver’s inability to handle lactic acid and compounds, is commonly seen in ESLD.